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Research Monograph

Semax (Synthetic ACTH(4-10) Analog)

Also Known AsSEMAX · Semax acetate · ACTH(4-10)-Pro-Gly-Pro

Molecular Weight813.93 g/mol
Discovered1982
Citations4 peer-reviewed
Research Areas5 domains
Background

Developed at the Institute of Molecular Genetics (Russian Academy of Sciences) in the late 1980s by Nikolai Myasoedov and colleagues. Semax is a synthetic heptapeptide analog of the ACTH(4-10) fragment with a stabilizing Pro-Gly-Pro C-terminal extension that confers resistance to enzymatic degradation. Approved in Russia and Ukraine as a nootropic and neuroprotective agent.

Amino Acid SequenceMet-Glu-His-Phe-Pro-Gly-Pro
Mechanisms of Action

How Semax Works

01

BDNF/TrkB Signaling

Semax robustly upregulates brain-derived neurotrophic factor (BDNF) expression and its high-affinity receptor TrkB in the hippocampus and cortex. TrkB activation triggers the MAPK/ERK and PI3K/Akt cascades, promoting neuronal survival, synaptic plasticity, and long-term potentiation (LTP).

BDNFTrkBMAPK/ERKPI3K/AktLTP
02

Melanocortin System Modulation

As an ACTH(4-10) derivative, semax interacts with melanocortin receptors (MC3R, MC4R, MC5R) without significant adrenocortical stimulation. This melanocortin signaling modulates neuroinflammation, attention, and learning through hypothalamic and limbic circuits.

MC3RMC4RMC5Rmelanocortin system
03

Neurotrophic Factor Expression

Beyond BDNF, semax upregulates NGF (nerve growth factor), GDNF (glial cell-derived neurotrophic factor), and their respective receptors. This broad neurotrophic response supports neurogenesis, axonal regeneration, and glial cell function in injury models.

NGFTrkAGDNFGFRalpha1
04

Immune Gene Modulation

Transcriptomic analyses reveal that semax modulates expression of chemokine and cytokine genes in the brain, including CXCL1, CCL3, and IL-6. This immunomodulatory profile contributes to reduced neuroinflammation and microglial activation in stroke and neurodegeneration models.

CXCL1CCL3IL-6microglia
Evidence-Graded Research Areas

Published Research

Strong
Moderate
Emerging
Preclinical

Cognitive Enhancement & Nootropic Effects

Moderate

Russian clinical studies demonstrate improved attention, memory consolidation, and executive function in healthy volunteers and patients with cognitive impairment. The mechanism involves BDNF-TrkB-dependent synaptic plasticity enhancement and increased cholinergic transmission. Semax is registered in Russia as a nootropic drug.

Ischemic Stroke & Neuroprotection

Moderate

Clinical use in Russia for acute ischemic stroke (intranasal administration within 6 hours of onset) has demonstrated reduced infarct volume and improved neurological outcomes in open-label studies. The neuroprotective mechanism involves BDNF upregulation, reduced excitotoxicity, and anti-inflammatory signaling. Western RCTs are not available.

Optic Nerve Neuropathy

Moderate

Russian clinical data support intranasal semax for optic nerve disease, with improvements in visual acuity and visual field in patients with optic nerve atrophy. The mechanism is attributed to NGF and BDNF-mediated support of retinal ganglion cell survival and axonal transport.

ADHD & Attention Disorders

Emerging

Preliminary clinical observations in children with attention disorders suggest improvements in sustained attention and behavioral regulation with semax nasal drops. The dopaminergic and melanocortinergic modulation may underlie attentional effects. Controlled trials with Western diagnostic criteria are lacking.

Neurodegenerative Disease

Preclinical

Preclinical models of Alzheimer's and Parkinson's disease show semax-mediated neuroprotection through BDNF upregulation, reduced amyloid-beta toxicity, and preserved dopaminergic neuron integrity. Transcriptomic studies demonstrate broad anti-inflammatory gene regulation in cerebral cortex after semax administration.

Safety Profile

Semax has been used clinically in Russia for over 25 years with an excellent safety profile. No significant adverse effects have been reported in published literature. It lacks adrenocortical stimulatory activity (unlike full-length ACTH), so it does not elevate cortisol. Mild nasal irritation with intranasal administration is the most commonly reported side effect. No dependency, tolerance, or withdrawal effects have been documented.

Handling & Storage

Semax is typically supplied as a lyophilized powder or as a pre-formulated nasal spray solution. Reconstitute lyophilized form with bacteriostatic water. Store reconstituted solution at 2-8°C and use within 30 days. Lyophilized powder stable at -20°C for 24+ months. N-Acetyl Semax Amidate is a modified analog with enhanced membrane permeability.

References & Citations

Peer-Reviewed Literature

  1. 1

    Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus

    Dolotov OV, Karpenko EA, Inozemtseva LS, et al.

    Brain Research, 2006PubMed 16978591DOI
  2. 2

    Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)

    Gusev EI, Skvortsova VI, Miasoedov NF, et al.

    Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 1997PubMed 9273752
  3. 3

    Novel insights into the protective properties of ACTH(4-7)PGP (Semax) peptide at the transcriptome level following cerebral ischaemia-reperfusion in rats

    Filippenkov IB, Stavchansky VV, Denisova AE, et al.

  4. 4

    Semax, an analog of ACTH(4-10), regulates expression of immune response genes during ischemic brain injury in rats

    Medvedeva EV, Dmitrieva VG, Limborska SA, et al.

    Molecular Genetics and Genomics, 2017PubMed 28321536DOI
Frequently Asked Questions

Semax FAQ

What is semax?

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH(4-10) fragment with a stabilizing Pro-Gly-Pro C-terminal tripeptide. Developed at the Russian Academy of Sciences, it is approved in Russia as a nootropic and neuroprotective agent. It strongly upregulates BDNF and other neurotrophic factors without affecting cortisol levels.

What is N-Acetyl Semax Amidate?

N-Acetyl Semax Amidate (NASA) is a modified analog of semax with an N-terminal acetyl group and C-terminal amidation. These modifications enhance resistance to enzymatic degradation and improve membrane permeability, potentially increasing bioavailability and CNS penetration compared to the parent compound.

How does semax differ from selank?

Both are Russian-developed heptapeptides, but they derive from different parent molecules and have distinct profiles. Semax is an ACTH(4-10) analog that primarily upregulates BDNF and acts as a nootropic. Selank is a tuftsin analog that primarily modulates GABA and acts as an anxiolytic. They are sometimes used together for complementary cognitive and anxiolytic effects.

What is the purity of G26x Peptides semax?

Our semax is 99%+ purity, independently verified by Janoshik Analytical with a full Certificate of Analysis (COA) available for each batch. Available as both standard semax and the N-Acetyl Semax Amidate analog.

How should semax be stored?

Lyophilized semax should be stored at -20°C for long-term storage (stable for 24+ months). Reconstituted solution should be stored at 2-8°C and used within 30 days. Intranasal solutions should be kept refrigerated between uses.

Available for Research

Semax Products

All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.

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Sem
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Semax

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Instant focus and brain power — delivers laser-sharp clarity, enhanced memory, and cognitive performance while building long-term brain health through BDNF.

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N-A
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Semax 2.0 — the upgraded form with enhanced brain penetration, stronger nootropic effects, and longer-lasting focus and cognitive performance per dose.

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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.